Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP-grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells’ activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.     

Between Cassirer and Kuhn. Some remarks on Friedman’s relativized a priori

This paper provides a critical evaluation of Friedman’s arguments in favour of a relativized a priori resting on Cassirer’s Neo-Kantianism, Reichenbach’s and Carnap’s constitutive a priori, and finally Kuhn’s account of scientific paradigms change. The main objection concerns Cassirer’s own view of dynamic and historical moveable a priori categories, which Friedman seems to underestimate and recasts in a merely regulative function. However, Cassirer conception of a “liberalized” a priori can shed new light on the process of scientific change and his transcendental method may be considered as a still stimulating alternative to Kuhn’s and post-Kuhnian relativism in the philosophy of science.     

Changes in the cardiac glutathione status after ischemia and reperfusion

Summary In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.This study was supported by a grant from Ministero Pubblica Istruzione and CNR Rome (no 8202331.56).     

Reversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP).

In a rat model of hemorrhagic shock which caused the death of all control rats within 30 min, i.v. injection of the ganglion-stimulating drug dimethylphenylpiperazinium (DMPP) caused a dose-dependent reversal of the shock condition--without the need for reinfusion of the shed blood--starting from the dose of 4 ng/kg i.v. Shock reversal was associated with the mobilization of residual blood and improvement in blood flow, particularly at the carotid level. These results could influence our thinking on pathophysiology and first-aid management of shock.     

Effects of pyrithiamine and oxythiamine on the thiamine content of tissues and blood pyruvate in mice

Riassunto La Piritiamina, somministrata per bocca in una singola dose di 0,5 mg a topolini di 12–14 g che ricevono 2 µg di tiaminapro die, non produce la sindrome neuromuscolare caratteristica dell'avitaminosi B₁ e non modifica nè la piruvicemia nè il livello di vitamina nel fegato, mentre lo fa abbassare nel muscolo e nel cervello. Se i topolini non ricevono tiamina, la stessa dose di Piritiamina dà perdita di peso, sindrome neuromuscolare in tutti gli animali trattati e cospicuo abbassamento del livello di vitamina B₁ nel cervello. Nelle stesse condizioni sperimentali, l'Ossitiamina, somministrataper os una sola volta in dosi di 0,5 e 2 mg, non dà alcuna sintomatologia neuromuscolare e non modifica nè il peso corporeo, nè il piruvato ematico, nè il contenuto in vitamina B₁ del muscolo e del cervello, solo abbassa il livello vitaminico del fegato.Questi risultati non sono in favore dell'ipotesi di una funzione della tiamina distinta da quella della cocarbossilasi.     

Reversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP)

In a rat model of hemorrhagic shock which caused the death of all control rats within 30 min, i.v. injection of the ganglion-stimulating drug dimethylphenylpiperazinium (DMPP) caused a dose-dependent reversal of the shock condition-without the need for reinfusion of the shed blood-starting from the dose of 4 ng/kg i.v. Shock reversal was associated with the mobilization of residual blood and improvement in blood flow, particularly at the carotid level. These results could influence our thinking on pathophysiology and first-aid management of shock.     

PcF protein from <Emphasis Type="Italic">Phytophthora cactorum</Emphasis> and its recombinant homologue elicit phenylalanine ammonia lyase activation in tomato

The phytotoxic protein PcF (Phytophthora cactorum-Fragaria) is a 5.6-kDa cysteine-rich, hydroxyproline- containing protein that is secreted in limited amounts by P. cactorum, an oomycete pathogen of tomato, strawberry and other relevant crop plants. Although we have shown that pure PcF triggers plant reactivity, its mechanism of action is not yet understood. Here we show that PcF, like other known fungal protein elicitors involved in pathogen-plant interaction, stimulates the activity of the defense enzyme phenylalanine ammonia a key step in understanding the mechanism of action of PcF at a molecular level is knowledge of its three-dimensional structure, we overexpressed this protein extracellularly in Pichia pastoris. The preliminary structural and functional characterization of a recombinant PcF homologue, N4-rPcF, is reported. Interestingly, although N4-rPcF is devoid of proline hydroxylation and has four additional amino acid residues attached to its N terminus, its secondary structure and biological activity are indistinguishable from wild-type PcF.Received 22 February 2003; received after revision 25 March 2003; accepted 14 April 2003     

The Systemic Approach of SSM: The Case of a Brazilian Company

This paper aims to describe the application of Soft Systems Methodology (SSM) to the reality of a Brazilian enterprise. Systemic practices are ways of putting to use systemic thought in the real world, using the precepts of the systemic approach, which is very important for knowledge management and globalization. The systemic practice SSM is used in the resolution of ill-defined problems, which often involve behavioral variables and, thus, cannot be addressed by the so-called hard methodologies. In this paper, SSM is applied to the problematic of a middle-market business, an auto supply distributor, whose managers consulted the authors of this paper as regards proposing improvements of its performance. As a result of this work, the authors were able to propose core changes in attitudes, leading to changes in structure and process.